The prevention of cisplatin-induced renal dysfunction by hydroxyl-containing dithiocarbamates.

Two hydroxyl containing dithiocarbamates, sodium N-methyl-D-glucamine dithiocarbamate (NaG) and sodium dihydroxyethyl dithiocarbamate (NaY) have been examined as agents for the control of the renal dysfunction in rats given cisplatin. Of these, NaG was found to be the more effective in controlling such renal dysfunction when administered at 1 and 3 h after 5 mg cisplatin kg-1, i.p. Renal function was examined 5 days after the administration of cisplatin by measurement of serum and urinary levels of creatinine and urea, creatinine clearance, serum and urinary levels of Na+, K+, Mg2+, Ca2+, as well as the concentrations of these ions in the renal medulla and cortex. Treatment of rats given cisplatin with NaG at 1 and 3 h post cisplatin resulted in indices of renal function which were not significantly different from those of animals which had received no cisplatin. The sole difference was found to be a slight increase in renal cortical Na+ concentration.     

Neurotoxic envenoming by an immigrant spider (Steatoda nobilis) in southern England.

A young woman was bitten on the shoulder by a female Steatoda nobilis spider, in Worthing on the south coast of England. She noticed intense radiating pain, local sweating (indicating parasympathetic stimulation) and feverishness. This immigrant species from the Canary Islands has established itself along the south coast of England in recent years. Like the related Mediterranean species S. paykulliana, S. nobilis may be of medical importance and deserves further study.     

Inhaled allergen-driven CD1c up-regulation and enhanced antigen uptake by activated human respiratory-tract dendritic cells in atopic asthma

Background Dendritic cells (DC) mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory‐tract DC (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD1 antigen presentation by hRTDC may contribute to asthma pathogenesis. Objective To investigate the influence of hRTDC on the balance between atopy and allergic asthma in human subjects and to determine whether CD1 expression by hRTDC is modulated during asthmatic inflammation. Methods Sputum cells were induced from steroid‐naïve, allergen‐challenged and allergen‐naïve subjects (atopic asthmatics, atopic non‐asthmatics and non‐atopic controls). hRTDC were identified using monoclonal antibody labelling and analysis by flow cytometry. Results hRTDC stained HLA‐DR⁺ (negative for markers of other cell lineages) were predominantly myeloid and comprised ∼0.5% of viable sputum cells. Sputum cells were potent stimulators of allogeneic CD4⁺ naïve T cells and enrichment/depletion experiments correlated stimulatory potency with DC numbers. Sputum contained cells that exhibited typical dendritic morphology when analysed by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of FITC‐dextran was enhanced in cells from asthmatics (P<0.001). Despite their increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and expressed increased levels of maturation markers (P<0.05–P<0.001), CD1c, CD1d and langerin (P<0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon in vivo allergen challenge (three to ninefold within 24 h; P<0.05). CD11c⁻CD123^high hRTDC were only detected in asthmatic sputum and were increased in number following allergen challenge. Conclusion Despite limited cell numbers, it proved possible to analyse human RTDC in induced sputum, providing evidence that increased antigen uptake and enhanced CD1 presentation by activated hRTDC may contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma may therefore constitute a novel target for future intervention strategies.     

Imipenem/cilastatin therapy of infections in cancer patients

Imipenem/cilastatin was administered during 153 febrile episodes occurring in cancer patients and the response rate was 68%. Considering only documented infections the response rate was 71%. Patients who received imipenem as initial therapy had a higher response rate than patients who received it after failing other antibiotics (77% versus 68%). The overall response rates for septicemias and pneumonias were 75% and 58%. Among the 57 gram-negative infections 77% responded, but the response rate was substantially higher if imipenem was used as initial therapy (94% versus 69%). The poorest response rate was observed when imipenem was given as secondary therapy for Pseudomonas infections (50%), but most of these patients had failed to respond to other appropriate antibiotics. The only serious side effect was seizures which occurred in ten patients, although eight of them had other predisposing factors. Imipenem appears to be a useful antibiotic for treatment of infections, even in neutropenic cancer patients.     

Hospital acquired native valve endocarditis caused by Acinetobacter calcoaceticus and treated with imipenem/cilastin

A case of hospital acquired endocarditis due to Acinetobacter calcoaceticus in a severely burned patient is presented. Both aortic and mitral native valves were affected and the organism was resistant to most antimicrobial agents.     

All-cause and cardiovascular mortality in diabetic subjects increases significantly with reduced estimated glomerular filtration rate (eGFR): 10 years' data from the South Tees Diabetes Mortality study.

AIMS: To investigate the association between estimated glomerular filtration rate (eGFR) and total and cardiovascular mortality in a population-based cohort of diabetic subjects. METHODS: A longitudinal study using a population-based district diabetes register comprising 3288 subjects in South Tees, UK. The eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) study equation. Patients were stratified by baseline eGFR into five stages as per the National Kidney Foundation guidelines: Stage 1, eGFR > 90; Stage 2, eGFR 60-89; Stage 3, eGFR 30-59; Stage 4, eGFR 15-29; and Stage 5, eGFR < 15 ml/min per 1.73 m(2). Main outcome was all-cause and cardiovascular mortality between 1 January 1994 and 31 July 2004. RESULTS: At baseline, mean age (58.4 years) differed between groups. Persons with lower eGFR were older (P < 0.001). Thirty-six percent (n = 1193, males 56%) had died by 10 years (cardiovascular cause in 60%). Median follow-up was 10.5 years amounting to 28 342 person years. Stages 4 and 5 (eGFR 相似文献   

Adherence to treatment in patients with epilepsy: associations with seizure control and illness beliefs.

OBJECTIVE: This study investigated non-adherence to antiepileptic drug treatment amongst patients with epilepsy in secondary care. The associations between adherence and seizure control, perceptions of illness and medication, anxiety and depression were also examined. METHODS: A cross-sectional study of fifty-four patients with epilepsy were recruited from a hospital epilepsy clinic. RESULTS: Fifty-nine percent were estimated to be non-adherent to medication. There was a negative correlation between adherence and frequency of seizures. Patients with poorly controlled epilepsy were more anxious, and expected a longer duration of their epilepsy. CONCLUSION: Assessment of adherence should be a routine part of management of epilepsy. Further recognition and support should be given to patients who have poor seizure control since they are more likely to be more anxious and have unhelpful illness and treatment beliefs.     

GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma.

Glucose is provided to cells by a family of glucose transport facilitators known as GLUTs. These transporters are expressed in a tissue specific manner and are overexpressed in many primary tumors of these tissues. Regulation of glucose transport facilitator expression has been demonstrated in endometrial tissue and endometrial adenocarcinoma. The following experiments were conducted to quantify and localize the expression of GLUT1 and GLUT8 in benign endometrium and compare this expression to endometrial cancer. Endometrial tissue samples were obtained from random hysterectomy specimens of patients with benign indications for surgery and endometrial cancer. Immunoblot and immunolocatization studies were performed using GLUT1 and GLUT8 specific antisera. Endometrial samples from 65 women who had undergone hysterectomy were examined (n=38 benign, n=27 malignant). A 44 and a 35.4 kDa immunoreacive species was demonstrated in endometrium and endometrial cancer for GLUT1 and GLUT8, respectively. Upregulation of GLUT1 expression was demonstrated with increasing grade of tumors (P<0.002). GLUT8 expression was increased in all tumor subtypes compared to atrophic endometrium (P<0.001). Apical localization by GLUT1 and GLUT8 was demonstrated in endometrial glands. GLUT1 and GLUT8 demonstrated diffuse intracellular localization in the cancer subtypes. GLUT1 and GLUT8 are expressed in both human endometrium and endometrial cancer. There appears to be a step-wise progression in GLUT1 and GLUT8 expression as tumor histopathology worsens. GLUT1 and GLUT8 may be important markers in tumor differentiation, as well as providing energy to rapidly dividing tumor cells.     

DLCO/Q and diffusion limitation at rest and on exercise in patients with interstitial fibrosis

Pulmonary diffusing capacity for carbon monoxide (DLCO) and pulmonary capillary blood flow (Qp) were measured on exercise in patients with a low DLCO with the aim of predicting, from the overall DL/Qp ratio, diffusion limitation for oxygen and relating it to the fall in arterial oxygen saturation actually observed. Five patients with cryptogenic fibrosing alveolitis (DLCO ranging from 20-54% predicted normal) exercised for 5 min at a work load equal to 60% of their maximum (45 to 90 watts). At 5 min (and previously at rest) they rebreathed rapidly for 15 sec from a 1.0 L bag containing helium (He), sulphur hexafluoride (SF6) and freon-22, 30% oxygen in argon and less than 1 ppm 11C-labelled carbon monoxide. Pulmonary capillary blood flow (Qp) and diffusing capacity (DLCO) were measured from flow-weighted breath-by-breath concentrations of freon-22 and 11CO, after correction for gas mixing delays (using He and SF6). Oxygen saturation (SaO2) (ear oximetry), MO2 and MCO2 and cardiac frequency were measured. PAO2 (ideal) was derived and mixed venous O2 saturation and content were calculated (Fick); PaO2 and PVO2 were derived from standard dissociation curves. For comparison, DLCO and Qp were measured in a similar fashion in five normal subjects exercising at 60 watts. Mean DLCO in patients with fibrosis was 9.62 (SD 2.88) ml.min-1, mm Hg-1 on exercise and mean Qp was 10.48 (SD 1.79) L.min-1 giving mean DLCO/Q ratios of 0.92 (SD 0.28). At 60 watts mean DLCO/Qp in normal subjects was 2.54 (SD 0.3), 2.76-times greater than in patients. SaO2% fell in patients by 3-15% on exercise. Predictions of alveolar-end capillary PO2 gradients from these overall DL/Q gradients showed that diffusion limitation accounted for 99% of the alveolar-arterial PO2 gradient on exercise in fibrosing alveolitis. Hughes (1991 Respir. Physiol. 83:167-178) [corrected] suggests that this simple approach overestimates the contribution of diffusion limitation by about 30%.